SUMMARY/ABSTRACT Lung cancer is the leading cause of cancer-related mortality in both men and women in United States with a dismal 5-year survival rate of 15%. While surgery is the only curative option, 70% of the patients are diagnosed with inoperable advanced disease, thus highlighting a lack of effective early screening methods. Typically, low dose computed tomography (LDCT) is used as the primary screening modality, however, 90-95% of suspicious lung lesions identified by LDCT eventually are found to be benign. As a result, such patients undergo medically unnecessary procedures and treatments, resulting in increased cost, time and morbidity. Hence there is an urgent need to develop a non-invasive complementary screening technique which can identify the high-risk population for lung cancer and thus enable detection of lung lesions at an early and potentially curable stage. To this end, cytological and molecular aberrations found in exfoliated bronchial epithelial cells in sputum of smokers have shown a strong correlation to lung cancer incidence. However, these diagnostically important cells represent less than 1% of the cellular composition of sputum, thus making their detection extremely challenging. Hence, it is essential to develop a method which can isolate and capture these scant yet important cells, while removing the other obscuring cells from sputum and thereby improve the clinical utility of these vital biospecimens. The goal of this Phase I application is to develop a novel peptide-coated glass slide, which can selectively capture and retain the epithelial cells of interest in a peptide-modified region, while moving the obscuring cells to a separate region of the slide. Epithelial cell capture on the peptide-modified slides will be first optimized to identify lead peptides for subsequent clinical testing. Thereafter compatibility of the peptide-modified slides with commonly employed clinical staining techniques will be established. Finally, the feasibility of using these peptide-modified slides for capturing cells from human sputum specimens will be validated. Successful completion of this project will not only allow for better visualization of the captured epithelial cells to the clinicians, but also enable further downstream processing of these cells to identify molecular and/or genetic atypia present, because of the non-destructive nature of this technology.